Chromatography is a technique used to, among other things, separate component elements of a starting material. Within the general field of chromatography, there are several types. Supercritical fluid chromatography (SFC) is a high pressure, reverse-phase method that typically operates above the critical point of the mobile phase fluid, and offers significant speed advantage and resolution over traditional techniques such as high performance liquid chromatography (HPLC). SFC employs carbon dioxide or another compressible fluid as a mobile phase, sometimes with a co-solvent, to perform a chromatographic separation. SFC has a wide range of applicability and typically uses small particle sizes of 3-20 microns for column packing material and is for analytical to preparative scale applications because of the lower pressure drop. In HPLC applications pressure at the top of the column typically reaches up to 1000 psi but pressure at the bottom is reduced to ambient pressure, creating a significant pressure drop.
Liquid chromatography (LC) applies to a cruder, lower pressure, lower performance technique for simple separations. Flash chromatography is a form of adsorptive chromatography and is subset of LC that uses a very simple, porous stationary phase with particle sizes nearer to 100 microns often in a disposable cartridge, or column. Because the particles in the packing material are larger and often irregular, the columns are much cheaper and are considered disposable. Pressure at the top of the column in flash chromato-graphy applications is typically up to 100 psi and dropping down to ambient at the bottom of the column. Still (U.S. Pat. No. 4,293,422) describes a method of adsorptive chromatography in which the mobile phase is first admitted into a space above an adsorbent bed of silica gel, then pushed through the bed with gas pressure. Once the space is cleared, the mobile phase with dissolved compounds for analysis is admitted, and it too is pushed into the bed, displacing the earlier charge of neat mobile phase. Then in a third step, a second charge of neat mobile phase forces the solution through the bed, causing fractionation of the solute. A subsequent disclosure by Andrews (U.S. Pat. No. 4,591,442) describes a similar device, the main difference being in the placement of the liquid holding space. Both disclosures focus on mechanical design and methods for achieving flash chromatography at relatively low pressure. More recently, Ritacco (US App. 2003/0102266) describes a convenient polymer-encased cartridge for use as a single ended flash chromatography column. Anzar (WO/2004-051257, US App. 2005/0287062) describes another type of pre-filled cartridge for flash chromatography. Common features of all of these disclosures are (1) an emphasis on instrumental convenience, and (2) the use of an adsorptive bed that allows for fast, although imprecise, separation of solutes. The disclosures also emphasize gas and liquid chromatography applications of low to moderate pressure.
The majority of all separations in flash chromatography use a normal phase technique with solvents such as methanol, ethanol, hexane, and heptane and occasionally the reverse phase technique with water and acetonitrile. Chemists buy thousands of flash chromatography systems per year to use primarily as a simple, repeatable normal phase purification technique. Because of the vast number of flash chromatography systems in medicinal chemistry laboratories in pharmaceutical research environments, users, insurers, regulators and environmentalists are growing increasingly concerned with the vast amount of toxic waste solvent generated at these sites. Given the obvious problems associated with unsafe, toxic, flammable solvents, a new simple, normal phase technique must be found that is fast and uses less toxic solvents.